There are known methods for generating monoclonal antibodies that are based on the isolation of B lymphocytes that produce antibodies targeting a particular antigen. These methods depend on the use of purified antigen or a mixture of antigens to identify and isolate B lymphocytes that bind that antigen (or antigens). Methods that depend on the use of antigen or mixtures of antigens to select antibody-forming cells (AFC) or B lymphocytes that express surface-receptors specific for an antigen, include using antigen-coated magnetic beads (Lagerkvist et al., 1995) or fluorochrome-labelled antigens and fluorescence activated cell-sorting (FACS) (Weitkamp et al., 2003) to isolate cells which have then been commonly expanded into clones. Monoclonal antibodies are then generated from these clones, for example by fusion to generate hybridomas (Steenbakkers et al., 1993) or by cloning of the genes encoding the antibody variable regions (e.g. using RT-PCR) (Lagerkvist et al., 1995; Wang & Stollar, 2000; Weitkamp et al., 2003). Alternatively, methods have been described to identify individual cells that are secreting antibody specific for a particular antigen, including using a hemolytic plaque assay with antigen-coupled erythrocytes, after which techniques such as RT-PCR can be used to clone the genes encoding the antibody variable regions (Babcook et al., 1996; U.S. Pat. No. 5,627,052 (1997) Schrader, J. W.). However, these strategies of identifying cells synthesizing antibodies specific for an antigen are not suitable for the generation of monoclonal antibodies against many desired target antigens, such as growth factor-receptors or other structures on the plasma membrane of cells that are not easy or possible to prepare in sufficient quantities in a pure or in a native state (e.g. native conformation may depend on appropriate post-translational modifications such as glycosylation). The state of the antigen is an important consideration because, for many applications, it is important to generate monoclonal antibodies that recognize the protein in its native configuration, for example if it is desired to generate an antibody that will neutralize a virus or toxin or bind some other biologically active substance. Moreover, methods that depend on isolating AFC using binding to specific antigen are not readily applied to the generation of libraries of monoclonal antibodies specific for the various unknown components of complex mixtures of substances such as those that occur on the surface of cells or viruses, or which are contained in a mixture of unknown compositions. Moreover, as described and currently practiced, methods based on the isolation of AFC using binding to antigen are confounded by failure to exclude cells that have bound antigen non-specifically, and from failure to exclude inadvertent co-isolation of the desired AFC together with a cell making a different antibody.